Wales face South Africa, Argentina, Tonga and Australia on consecutive weekends in November with Gatland including the uncapped Rhodri Williams and Cory Allen in his squad for the first time.
The two players, who both have plenty of experience with Wales Under 20 and in Allen's case with Wales Sevens, feature alongside fellow young guns Rhys Patchell and Eli Walker while Luke Charteris, Aaron Jarvis and Rhys Priestland make welcome returns from injury.
Jamie Roberts and Alex Cuthbert miss out with knocks while James Hook, Paul James and Emyr Phillips are all included. Gatland's squad contains many of the usual faces but with Williams and Allen selected, the Wales head coach is looking forward to seeing how they fare in the senior environment.
"We've picked a squad of players, some of whom are injured, some of whom have been with the Lions and some youngsters as well," he said.
"It's a countdown before the next World Cup. We've picked a larger squad as part of wanting to put out a strong side against South Africa, Australia and Argentina and perhaps giving one or two of those less experienced players an opportunity in the Tonga game."
Asked about the selection of Williams and Allen, Gatland added: "They are both talented players. We've been watching Cory for a while, especially with the sevens.
"He's carrying a bit of a knock at the moment as is Owen Williams so we've got some strength but we need to develop some depth as well.
"We have to assess where every player is. The Lions players are excited to come back into the Welsh set up but it's hard to see where they are until they come back into camp."
Gatland has been hampered by the loss of Cuthbert and Roberts but is hopeful the former may be able to play a part as he undergoes scans. British & Irish Lions skipper Sam Warburton leads the squad and is joined by a wealth of experience with Dan Lydiate, Toby Faletau, Justin Tipuric and Ryan Jones offering alternative back row options.
"Jamie may be available for the last game and Alex needs some more scans, it looks like there's been a ligament pulled away," Gatland added.
"Sam is still a young man and he equipped himself superbly on the Lions tour. It's an attritional position and with Justin Tipuric too, we're lucky we've got two world class players in that area. If one of them is injured, the other can step in or we could play one at six and one at seven as we did in the England game."
After the squad announcement, Wales' preparations now swing into action ahead of their first clash with the Springboks in just over two weeks.
"The information coming to us is that South Africa would have liked us later on and that's a sign of respect to the talent we have in our squad," said Gatland.
"We might be able to catch them cold but they're always tough, always physical and we want to hit the ground running.
"Hopefully we can start the autumn off with a good performance and a good result."